Photodynamic therapy is a minimally invasive two-step medical procedure that uses light-activated agents called photosensitizers to treat a range of diseases involving rapid cell growth, such as cancerous tumors or abnormal blood vessels. In one instance, a photosensitizer is administered and, once in the bloodstream, associates with lipoproteins. Rapidly dividing cells require more lipoproteins than normal cells, thus a higher concentration of the drug accumulates in these tissues. The photosensitizer is then activated by exposure to light containing a wavelength which activates the photosensitizer. Once activated, the photosensitizer converts oxygen found in the cells into highly energized singlet oxygen. Singlet oxygen can react with subcellular components such as proteins and lipids, which disrupts normal cellular function and results in killing the cells. Lasers and fiber optics are used to deliver the activating light.
Photolysis of a photoactivatable moiety generates an intermediate which reacts to result in a crosslink to another molecule. Several classes of reactive intermediates have been exploited in photoaffinity labeling; the predominant ones being nitrenes, radicals and carbenes. Nitrenes stemming from aryl azides have been studied extensively and appear throughout the literature. Scheme A below shows that irradiation produces a singlet nitrene that intersystem crosses to the ground state triplet (at low temperatures, some chemistry from the singlet is observed to form 2). The triplet nitrene is expected to behave like a diradical, and is hoped to effect useful binding by hydrogen abstraction then radical coupling (Schuster, G. B.; Platz, M. S. Adv. Photochem. 1992, 17, 69-143). 
A representative example of the use of azides in photoaffinity labeling is found in the work of Swindell et. al. (Swindell, C. S.; Heerding, J. M.; Krauss, N. E. J. Med. Chem. 1994, 37, 1446-1449). A photoaffinity taxol analogue that bears an azide photoreactive moiety in the A-ring side chain of taxol was used to label the N-terminal domain of β-tubulin with specificity.
Radical intermediates are ideally suited for photoaffinity labeling. They are known to abstract hydrogen atoms from virtually any site, are more reactive with C—H bonds than are nitrenes and have less propensity for intramolecular rearrangements than carbenes. Examples of radical generating photoprobes include benzophenone (Dorman, G.; Prestwich, G. D. Biochemistry 1994, 33, 5661-5673), enones (Boyd, N. D.; Cerpa, R.; Kaiser, E. T.; Leeman, S. E.; White, C. F. Biochemistry 1991, 30, 336-342), and various diazo/diazonium compounds whereby loss of N2 results in the reactive intermediate (Ehret-Sabatier, L.; Kieffer, B.; Goeldner, M. Hirth, C. NATO ASI Ser., Ser. C; Photochem. Probes Biochem. 1989, 272, 107-122).
Diazirines are capable of generating carbenes as reactive intermediates. Most of the recent work with diazirines exploits the photochemical reactivity of the trifluoroethyldiazirinephenyl group (Brunner, J.; Senn, H.; Richards, F. M. J. Biol. Chem. 1980, 255, 3313-3318). Irradiation of a substituted diazirine (4) (Scheme B below) has been shown to give carbene (5) and the corresponding diazo compound (6). 
Carbenes have the ability to insert into carbon-hydrogen bonds (Sol-H) to yield products like 7. The diazirine unit is small, non-bulky, and lipophillic. It has a chromophore that extends significantly into the 300 nm range. Many applications of photo cross-linking have been reported for this functionality. Shih et al. (Anal. Biochem. 1985, 144, 132-141) reported the synthesis, radioisotopic labeling, and resolution of a phenylalanine analog, 3-[p-[3-(trifluoromethyl)-3H-dizirin-3-yl]phenylalanine (8), containing the 3-(trifluoromethyl)-3H-diazirinyl group. Like all diazirines, 8 absorbs in the near UV (λmax 350; ε 265). 
Photodynamic therapy is a relatively safe treatment, because without exposure to light, the drug has no effect. Furthermore, the drug accumulates primarily in diseased cells as described above, thus upon irradiation the effects on surrounding healthy tissue are minimized.
Effective photosensitizers include porphyrogenic compounds with strong absorption coefficients at wavelengths in the red region of the electromagnetic spectrum. At this wavelength, human tissue is the most transparent to light, and allows efficient excitation of the photosensitizer drug, causing the most phototoxic effect (Potter, W. R. In Proceedings of SPIE 1989, 1065, 88). Unfortunately, red light is present in ambient daylight, and patients who undergo PDT experience varying degrees of skin photosensitivity resulting from residual photosensitizer in healthy tissue. Depending upon the rate of elimination of a particular photosensitizer, this period of skin photosensitivity can range from a day or two to several weeks. This side effect of PDT has prompted an exploration of possible structural modifications of the photosensitizers, and new ways of using visible light for their photoactivation.
Citation of the above documents is not intended as an admission that any of the foregoing is pertinent prior art. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.